We respond to the "Brain Disorders in the Developing World: Research Across the Lifespan" FOA (PAR-08- 113), issued jointly by the Fogarty Institute and other NIH units including the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Environmental Health Sciences. Researchers at the Mount Sinai School of Medicine, Harvard Medical School, the University of Cincinnati, the University of Guadalajara (Mexico), and the Instituto Nacional de Salud Publica (Mexico) request funding to initiate and sustain a durable research program in Mexico focusing on the impact of environmental factors on child neurodevelopment. Training will be provided by US researchers in three domains: neurodevelopmental assessment using the NICU Neurobehavioral Network Scale and Bayley Scales of Infant Development;design of children's environmental health research studies;and epigenetic methods. The training will be applied in a pilot cohort study of prenatal methylmercury exposure in subsistence fishing communities around Lake Chapala, the largest watershed in Mexico where preliminary studies have documented moderate and ongoing fish contamination;elevated hair mercury levels among one-fourth of women of childbearing age;and strong associations between fish consumption and hair mercury levels. Pilot data will serve as the cornerstone for a larger cohort which will examine whether elevations in hair mercury levels are associated with decrements in NICU Neurobehavioral Network Scale and Bayley Scales of Infant Development. Biospecimens will be analyzed to assess for the presence of potential confounders, including: lead, arsenic, persistent organic pollutants;and control for fish consumption will be made using questionnaire data. To assess possible genetically determined variation in susceptibility to MeHg, we will measure metallothionein expression in maternal and cord blood as well as maternal and fetal genotypes of six mercury detoxifying genes, i.e. GSTM1, GSTP1, GSTT1, GCLC, GCLM and CPOX . The Lake Chapala population offers major advantages for study of prenatal MeHg toxicity over previous cohorts including: more moderate exposure than in the Seychelles or Faroe Islands thus more closely approximating current exposure levels in the US population, absence of potentially confounding PCB contamination, opportunity to use culturally validated test instruments, a homogenous population for genetic investigations, geographic stability of population, and lower costs of implementation. The project draws upon the expertise of one of two locations in the US leading implementation of the National Children's Study, a Fogarty-funded International Research and Training Program in Environmental and Occupational Medicine, and an NIEHS-funded Children's Environmental Health and Disease Prevention Research Center. PUBLIC HEALTH RELEVANCE: Controversy remains as to the danger posed by prenatal exposure to methylmercury, a common contaminant of seafood. The proposed pilot cohort study endeavors to study the potential harm posed to child development, and to empower Mexican researchers with the capacity to pursue other studies of environmental risk factors to early brain development.